Multiple sclerosis is a disease that characteristically shows demyelination, in which myelin sheaths covering nerve fibers of the brain, spinal cord, optic nerves, and the like are destroyed. In this disease, progression of disorders occurs while recurrence and remission are repeated. It is known that the symptoms of this disease vary depending on the lesion area, and examples of the symptoms include various nervous symptoms such as visual impairment, quadriplegia, sensory disturbances, and gait disturbances (Aranami et al., Cell Technology, Vol. 30, No. 10, 2011, pp. 1060-1063).
As therapeutic agents for multiple sclerosis, adrenocortical hormones (steroids) are used for acute-phase treatment, and interferon β-1b and interferon β-1a are used for prevention of recurrence (Kira et al., “Multiple Sclerosis Treatment Guidelines 2010,” 2010, pp. 11-15).
Multiple sclerosis shows enhancement of the coagulation system, and it is known that the symptoms can be ameliorated with a thrombin inhibitor hirudin in a disease model for multiple sclerosis (Han et al., Nature, Vol. 451, 2008, pp. 1076-1081).
WO 2011/126903 reports a low molecular weight compound having thrombin inhibition activity. However, WO '903 does not show usefulness of the compound against multiple sclerosis, and shows no specific data on its pharmacological effect.
On the other hand, cyclohexane derivatives represented by the Formula below are known to be effective as an analgesic and therapeutic agent for neurogenic pain (WO 2010/050577), therapeutic agent for fibromyalgia (WO 2011/125836), therapeutic agent for urine storage dysfunction (WO 2011/125838), therapeutic agent for Alzheimer's disease (WO 2011/136318), and therapeutic agent for neuropathic pain (WO 2012/015027):
wherein
A represents substituted or unsubstituted 1,5-diaryl-1H-pyrazol-3-yl, 4,5-diaryloxazol-2-yl, or the like;
R4 represents a fluorine atom, hydroxyl, or the like; and
R5 and R6 each independently represent a hydrogen atom, hydroxyl, carboxyl, or the like.
When a steroid is used in treatment and prophylaxis of multiple sclerosis, amelioration of acute-phase symptoms can be seen. However, its effect is transient and long-term treatment is difficult. Interferon β-1b and interferon β-1a are used to prevent recurrence of multiple sclerosis. Since these are biological preparations, they are expensive. However, their therapeutic effect cannot necessarily be expected for all patients and those preparations are known to be ineffective for some patients (Aranami et al., Cell Technology, Vol. 30, No. 10, 2011, pp. 1060-1063 and Kira et al., “Multiple Sclerosis Treatment Guidelines 2010,” 2010, pp. 11-15).
It could therefore be helpful to provide a method of treating or preventing multiple sclerosis.